Gerald Lyman is speaking with his oncologist, Dr. Dale Shepard, during his cancer treatment that happens every 3 weeks at the Cleveland Clinic. Back in 2013, Lyman was diagnosed with stage 4 bladder cancer, with little chance of survival.

When chemotherapy and experimental drugs didn’t work, he opted to try a clinical trial for a medicine designed to harness his immune system to fight the cancer – a new category of treatment known as immunotherapy. According to Dr. Shepard, Lyman was one of the first patients to try a new drug to treat the tumor that engulfed his bladder. And after about a month of treatment, he presented a big surprise.

"He comes in and says I think this is working, I think I’m peeing out my tumor," Shepard said. "And he proceeds to pull out a zip lock bag with little strands of tissue. I of course send it to pathology and sure enough, it was his tumor… That was about a month of therapy. It just dissolved the tumor."

Lyman is what’s known as an exceptional responder — a patient who experiences a powerful response to a new cancer treatment, while most other patients on the trial don’t.

Part of Dr. Shepard’s job is to explain to patients who want to volunteer for experimental treatments with new immunotherapy drugs that there is no guarantee they’ll work for them.

"One of the interesting things of this particular class of compound, is they don’t work with everyone and we don’t know why," Shepard said.

But finding out why they do work on certain patients is the goal behind the Exceptional Responders Initiative at the National Cancer Institute. A 2014 study that focused on an exceptional responder with bladder cancer discovered two genetic mutations that may have played a role in their powerful response. Now, researchers are gathering data from as many cases as they can to dig into the underlying reasons behind why certain patients like Lyman respond so well, says Dr. Barbara Conley, Associate Director of the Cancer Diagnosis Program at the National Cancer Institute.

"So we thought well what if we could understand the molecular features of those tumors. Could that lead us to use these drugs in a more targeted way," Conley said.

Conley says the next steps are to analyze the exceptional responder cases they’ve gathered, hopefully providing some results within the year.

At the end of each visit, Dr. Shepard always discusses potential side effects of the drug with Gerald Lyman. For Lyman, being an exceptional responder has meant having a new lease on life. As his daughter waits with him for the treatment to finish, he talks about the joy of riding his bike again.

"I ride a bicycle a lot," Lyman said. "For two years I didn’t ride at all. So last year I rode quite a bit, didn’t I? I’ll ride a lot more this summer."

While doctors don’t know how long Lyman’s therapy will continue to work, one thing they do know is that research into cases like his will help play a key role in developing new therapies.